Epigenetic alterations of chromosome 3 revealed by NotI-microarrays in clear cell renal cell carcinoma.
Epigenetic alterations of chromosome 3 revealed by NotI-microarrays in clear cell renal cell carcinoma.
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DOI：
10.1155/2014/735292
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发表时间：
2014
影响因子：
--
通讯作者：
Kashuba VI
中科院分区：
文献类型：
--
作者：
Dmitriev AA;Rudenko EE;Kudryavtseva AV;Krasnov GS;Gordiyuk VV;Melnikova NV;Stakhovsky EO;Kononenko OA;Pavlova LS;Kondratieva TT;Alekseev BY;Braga EA;Senchenko VN;Kashuba VI
本研究旨在阐明肾癌发生过程中的表观遗传学和遗传学改变。原始方法包括3号染色体特异性NotI微阵列，其含有与188个基因相关的180个NotI克隆，用于与原发性透明细胞肾细胞癌（ccRCC）的23对正常/肿瘤DNA样本杂交。22个基因在17-57%的肿瘤中显示甲基化和/或缺失。这些基因包括肿瘤抑制基因或候选基因（VHL、CTDSPL、LRRC 3B、ALDH 1 L1和EPHB 1）和先前不被认为与癌症相关的基因（例如，LRRN 1、GORASP 1、FGD 5和PLCL 2）。亚硫酸氢盐测序分析证实甲基化是ccRCC中的常见事件。建议使用一组六种标志物（NKIRAS 1/RPL 15、LRRN 1、LRRC 3B、CTDSPL、GORASP 1/TTC 21 A和VHL）用于肾活检中的ccRCC检测。使用定量PCR显示ccRCC中6个NotI相关基因的mRNA水平降低：LRRN 1、GORASP 1、FOXP 1、FGD 5、PLCL 2和ALDH 1 L1。大多数检测的基因在ccRCC和乳头状RCC中表现出不同的表达谱。ALDH 1 L1基因在ccRCC和乳头状RCC中的下调程度和频率最强。此外，ALDH 1 L1 mRNA水平下降的程度在两种组织学类型的RCC III期与I期和II期相比更明显（P = 0.03）。FGD 5基因在肾细胞癌中的表达与肾组织中的表达有显著性差异（P < 0.06）。 谨以此纪念尤金·R.扎巴罗夫斯基
This study aimed to clarify epigenetic and genetic alterations that occur during renal carcinogenesis. The original method includes chromosome 3 specific NotI-microarrays containing 180 NotI-clones associated with 188 genes for hybridization with 23 paired normal/tumor DNA samples of primary clear cell renal cell carcinomas (ccRCC). Twenty-two genes showed methylation and/or deletion in 17–57% of tumors. These genes include tumor suppressors or candidates (VHL, CTDSPL, LRRC3B, ALDH1L1, and EPHB1) and genes that were not previously considered as cancer-associated (e.g., LRRN1, GORASP1, FGD5, and PLCL2). Bisulfite sequencing analysis confirmed methylation as a frequent event in ccRCC. A set of six markers (NKIRAS1/RPL15, LRRN1, LRRC3B, CTDSPL, GORASP1/TTC21A, and VHL) was suggested for ccRCC detection in renal biopsies. The mRNA level decrease was shown for 6 NotI-associated genes in ccRCC using quantitative PCR: LRRN1, GORASP1, FOXP1, FGD5, PLCL2, and ALDH1L1. The majority of examined genes showed distinct expression profiles in ccRCC and papillary RCC. The strongest extent and frequency of downregulation were shown for ALDH1L1 gene both in ccRCC and papillary RCC. Moreover, the extent of ALDH1L1 mRNA level decrease was more pronounced in both histological types of RCC stage III compared with stages I and II (P = 0.03). The same was observed for FGD5 gene in ccRCC (P < 0.06). Dedicated to thememory of Eugene R. Zabarovsky
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影响因子：
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DOI：
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发表时间：
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影响因子：
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